Pesce John T, Liu Zhugong, Hamed Hossein, Alem Farhang, Whitmire Jeanette, Lin Hongxia, Liu Qian, Urban Joseph F, Gause William C
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2008 Jan 1;180(1):464-74. doi: 10.4049/jimmunol.180.1.464.
Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however, little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared with wild-type mice, elevations in a Gr-1bright population in the draining lymph node was significantly decreased in CCL2-/- mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1+ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1bright population was comprised of neutrophils expressing TGF-beta and TNF-alpha. Following Gr-1+ cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-gamma, increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1+ cell-depleted mice with N. brasiliensis larvae that were pretreated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance.
感染寄生线虫巴西日圆线虫会诱导强烈的Th2反应；然而，对于可能有助于保护性免疫的先天反应早期阶段却知之甚少。为了研究该反应中的早期事件，在接种巴西日圆线虫后检测了引流淋巴结中的趋化因子表达。观察到包括CCL2在内的几种趋化因子明显增加。与野生型小鼠相比，接种巴西日圆线虫后，CCL2基因敲除小鼠引流淋巴结中Gr-1bright细胞群的增加显著减少。进一步的流式细胞术和免疫荧光分析表明，在野生型小鼠中，Gr-1+细胞在接种巴西日圆线虫后不久短暂进出引流淋巴结。Gr-1bright细胞群由表达转化生长因子-β和肿瘤坏死因子-α的中性粒细胞组成。在Gr-1+细胞耗竭后，巴西日圆线虫感染导致干扰素-γ水平短暂但显著升高、血清IgG2a增加、Th2细胞因子和血清IgE减少、死亡率大幅增加以及蠕虫排出延迟。此外，在重要器官中很容易检测到细菌。用抗生素预处理的巴西日圆线虫幼虫感染Gr-1+细胞耗竭的小鼠可防止细菌传播、Th1炎症反应以及宿主存活率下降。这项研究表明，寄生线虫可能是潜在有害细菌的重要载体，而这通常由CCL2依赖的中性粒细胞控制，这些中性粒细胞可确保Th2免疫反应和寄生虫抗性的最佳发展。
